DESCRIPTION: Tamoxifen is beneficial for treatment of breast cancer, but is associated with a marked increased risk of uterine cancer. With over 1,000,000 women worldwide taking tamoxifen, uterine surveillance has become a major clinical issue. There are currently few data on the value of routine uterine screening to detect premalignant uterine pathology in asymptomatic women or diagnostic testing in women with abnormal uterine bleeding. Early detection and treatment of premalignant disease may prevent uterine cancer, but screening and treatment protocols have not been established. We propose a cross-sectional study to collect pilot data on prevalence of endometrial pathology and a brief prospective cohort study to determine response to treatment of premalignant uterine pathology in 100 women with a uterus who have breast cancer and are taking tamoxifen. We will also obtain pilot data on the accuracy of screening and diagnostic testing with endovaginal ultrasound (EVS) and magnetic resonance imaging (MRI) to detect abnormal uterine pathology. Women will be recruited from the UCSF/Mount Zion Breast Care Center and the UCSF Medical Oncology Clinic which currently care for 175 women receiving tamoxifen. All women on tamoxifen for at least one year will be asked to participate in this study and undergo EMB, EVS, and MRI. If premalignant uterine pathology is found, women may 1) continue tamoxifen, 2) discontinue tamoxifen, 3) continue tamoxifen and add a progestin, 4) discontinue tamoxifen and add a progestin, or 5) undergo hysterectomy. The choice of treatment will be left to the woman and her physicians and will be depend on her estimated benefit of tamoxifen and the risk associated with her specific endometrial abnormality. The EMB, EVS, and MRI will be repeated in 3 months to evaluate treatment response. This pilot study data will allow us to assess the magnitude of the clinical problem of premalignant uterine pathology and will provide preliminary data on the accuracy of EVS and MRI for screening and diagnosis, using endometrial biopsy (EMB) as the gold standard, in women with breast cancer taking tamoxifen. It will also provide estimates of the effectiveness of treatments for premalignant uterine pathology. These pilot data will not provide adequate statistical power to evaluate our research questions, but will allow planning of a longitudinal study of incidence of uterine pathology, accuracy of screening tests, and response to treatment.